Malignant tumours are traditionally treated by either of three techniques: surgery, radiation or chemotherapy. Often combinations of these techniques are necessary. By surgery, larger tumours of suitable locations may be removed. Surgery alone is however often not enough, due to residues of cancerous tissues and twin tumours. Radiation is used for smaller tumours, particularly in difficult-to-reach locations. By using radiation techniques, surgery may not be necessary. Chemotherapy suffers from other side effects, including necrotic effects on non-cancerous cells.
A therapeutic procedure explored in some fields of surgery is to generate heat in vivo at specific locations in the body, and to benefit from the heat for therapeutic purposes, such as the treatment of cancer cells. Local heat may be achieved by several methods, e.g. with catheters equipped with elements generating heat by electrical resistivity, which can be controlled to desired locations via the vascular system.
An alternative technique to achieve heat in-vivo, is to apply small volumes of slurries or pastes of heat generating materials at the desired locations, e.g. by injection with needles. The material cures injected into the body cures through exothermal chemical reactions and thereby generates the desired temperatures. As the temperature rises, local therapeutic effects are generated. Ideally, when the reactions are completed, the cured substance should form a biocompatible solid material, which can be left for prolonged periods of time in the body without any negative health effects. Only a few types of therapies benefiting from heat generating materials are performed today; the heat generating material being PMMA (polymethylmethacrylate) bone cement, despite the lack of biocompatibility.
Treatment of malignant cancerous tumours, as well as metastasis, myeloms, various cysts, etc, involving the local application of heat generating materials in vivo is used to some degree, although it is still a less frequent treatment technique. The technique involves either local thermal necrosis or restriction of the nutritional or blood feed, or oxygenation, to the tumours or cells.
The use of injectable heat generating materials for cancer treatment is particularly suitable for tumours in the skeleton. The procedure may involve direct injection of a cell-destroying cement; or alternatively the removal of the tumour by surgery, followed by filling of the remaining cavity by an in-situ-curing material. The former procedure offers at least two advantages: One being that increased temperatures during curing reduce the activity of, or kills, residual cancerous tissue. Another effect is that the cement restores the mechanical properties of the skeleton, hence reducing the risk of fractures due to weakened bone.
Injectable pastes are also used in combination with radiation treatment, as when spine vertebrae are first filled with PMMA bone cement injected into the trabecular interior through the pedicles to provide mechanical stability, followed by radiation treatment of the same vertebra.
Similarly, injectable pastes are used for the treatment of collapsed osteoporotic vertebrae. The filling of collapsed vertebrae with bone cement reduces the pain and the dimensions of the vertebrae may be restored. Here the heat generation contributes, in addition to the mechanical stabilization of the vertebrae to the reduction of pain in the spine.
Locally generated heat can be used for the local destruction of nerves to reduce pain, to destroy the function of blood vessels, and to locally trigger the effect of drugs.
As of today, there is no commercialised biocompatible cement, specifically developed for therapeutic purposes by heat generation. Only standard bone cement based on polymethyl methacrylate (PMMA) is used. This material may generate sufficient temperatures, but does not show adequate biocompatibility. Due to lack of better alternatives, PMMA bone cement is however well established in surgery.
Disadvantages With Present Materials
Today's PMMA based bone cements are developed for orthopaedic needs, primarily the fixation of hip and knee implants in the skeleton. Despite many disadvantages, these materials are today established in orthopaedics after several decades of use. There is however an on-going search for better, more biocompatible bone cements.
PMMA based bone cements are not biocompatible materials. They have clear toxic effects caused by leakage of components, such as solvents and non-polymerised monomer. These leakages become particularly high for low viscosity formulations (being injectable) with high amounts of solvents and monomers.
Ideally in cell therapy with heat generating pastes, the volume of cured material left after therapy, shall trigger a minimum of unwanted tissue reactions. This requires a high degree of chemical stability and biocompatibility.
For treatment of cancerous bone, the cured material left in the skeleton ideally possesses mechanical properties similar to those of natural bone. In particular, an insufficient strength or stiffness is disadvantageous for load bearing parts of the skeleton. An orthopaedic cement shall preferably have an elastic modulus of around 10–20 GPa. Today's PMMA bone cements show elastic modulus around 3 GPa.
Today's PMMA bone cements cure while generating heat in amounts considered excessive for normal orthopaedic use. For use in vertebroplasty, some argue that a temperature rise may be advantageous, since it may contribute to reduce pain. However, today's bone cements offer no, or very limited, possibilities for the surgeon to control the generated temperature.
Also cements generating low temperatures rises during curing are of interest. A low temperature bone cement based on hydraulic ceramics is described in the pending Swedish patent application “Ceramic material and process for manufacturing” (SE-0104441-1), filed 27 Dec. 2001. In said patent application the temperature rise due to the hydration reactions is damped by addition of suitable inert, non-hydraulic phases, which are also favourable for the mechanical properties and biocompatibility. However, these ceramic materials do not offer the means to control the heat generation through well controlled phase compositions of the hydrating ceramic, or controlling the temperature by accelerators and retarders.